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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disseminated intravascular coagulation (DIC) can be caused by a variety of diseases. Experimental models of DIC have provided substantial insight into the pathogenesis of this disorder, which may ultimately result in improved treatment. Disseminated coagulation is the result of a complex imbalance of coagulation and fibrinolysis. Simultaneously occurring tissue factor-dependent activation of coagulation, depression of natural anticoagulant pathways and shutdown of endogenous fibrinolysis all contribute to the clinical picture of widespread thrombotic deposition in the microvasculature and subsequent multiple organ failure. Cornerstone for the treatment of DIC is the optimal management of the underlying disorder. At present, specific treatment of the coagulation disorders themselves is not based on firm evidence from controlled clinical trials. Plasma and platelet transfusion are used in patients with bleeding or at risk for bleeding and low levels of coagulation factors or thrombocytopenia. The role of heparin and low molecular weight heparin is controversial, but their use may be justified in patients with active DIC and clinical signs of extensive fibrin deposition such as those with meningococcal sepsis. There is some evidence to indicate that low molecular weight heparin is as effective as unfractionated heparin but may be associated with a decreased bleeding risk. Antithrombin III (AT III) replacement appears to be effective in decreasing the signs of DIC if high doses are administered, but effects on survival or other clinically significant parameters are at best uncertain. If AT III supplementation is used, the dosage should be selected to achieve normal or supranormal plasma levels of 100% or higher. Results of studies on protein C concentrate, thrombomodulin or inhibitors of tissue factor are promising, but the efficacy and safety of these novel strategies remains to be established in appropriate clinical trials.
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PMID:Current drug treatment strategies for disseminated intravascular coagulation. 961 92

With the purpose of assessing the part DIC syndrome has in hemorrhage, blood coagulation system was studied in patients presenting with gastrointestinal hemorrhage. Thrombin, a blood coagulation IIa factor, which is one of the chief markers of DIC syndrome, has been found in great amounts in blood in 50% of cases. But this did not lead to disseminated transformation of fibrinogen to fibrin because of the action of the inhibitor of coagulation during the stage of activation of fibrinogen by thrombin. Antithrombin III had but a minor part in these processes. It is suggested that rise in concentration of thrombin that is not accompanied by formation of disseminated fibrin might be of compensatory and adaptive significance. Another characteristic of blood coagulation system in the patients is depressed plasminolysis, while increase, against this background, in concentration of products of fibrin/fibrinogen degradation that is most common, reflects disturbance in the processes of their elimination from the bloodstream.
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PMID:[The characteristics of the DIC syndrome in gastrointestinal hemorrhages]. 962 39

Antithrombin III (ATIII) and protein C (PC) are major inhibitors of the coagulation cascade and might regulate the cytokine network. We tested the possibility that a combined supplementation using these two inhibitors might have synergistic effects on sepsis-induced disseminated intravascular coagulation and shock. Hemodynamics, coagulation parameters, tumor necrosis factor (TNF) alpha, and interleukin 6 levels were measured in pigs submitted to a bolus infusion of Escherichia coli endotoxin (lipopolysaccharide). Four groups were studied: control lipopolysaccharide, ATIII (100 IU/kg), PC (50 IU/kg), and ATIII-PC (same doses). The endotoxin infusion resulted in a typical hypokinetic shock with disseminated intravascular coagulation in all animals. Compared with the control group, a significant improvement in mean arterial pressure and systemic vascular resistance was observed in the PC and ATIII-PC groups. The increase in lactate levels was almost completely blunted in the PC group. A significant lesser increase in TNFalpha levels was observed in the ATIII-PC group. No effects were seen on interleukin 6 levels. Coagulation and fibrinolysis parameters were not improved by ATIII and/or PC, except for a lesser decrease in prothrombin time in the ATIII-PC group. We conclude that in this acute endotoxic model, a combined supplementation using PC and ATIII concentrates has favorable effects on hemodynamic parameters and TNFalpha levels, independently from the anticoagulant actions of these inhibitors.
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PMID:Effects of a combined antithrombin III and protein C supplementation in porcine acute endotoxic shock. 984 Jun 53

The physiological inhibitor of thrombin, antithrombin III (ATIII, Kybernin P) was investigated for its antiinflammatory and anticoagulant effects in a pig model of septic shock. Pigs were infused with a dose of 0.25 microgram. kg-1. h-1 of lipopolysaccharide (LPS) over a period of 3 hours. Animals developed systemic inflammation, disseminated intravascular coagulation (DIC), organ failure and cardiovascular abnormalities, namely pulmonary hypertension and systemic hypotension. Twenty septic pigs were allocated to 2 study groups, treated either with ATIII (n=10) or placebo (n=10). ATIII was administered as a 250-U/kg IV bolus infusion for 30 minutes (-60 to -30 minutes) followed by a single IV bolus of 125 U/kg (t=0) and a second 30-minute infusion of 250 U/kg (120 to 150 minutes). ATIII significantly prevented the development of a DIC; the increase in fibrin monomers (placebo, 11.4+/-9.1 reciprocal titers, at 6 hours) was completely overcome by ATIII (P<0. 05). ATIII significantly prevented the increase in thromboxane (TXB2) levels, which were 809+/-287 pg/mL in the placebo and 420+/-174 pg/mL in the verum group after 6 hours (P<0.02). On the other hand, ATIII had no influence on TNF levels. In a lethal study with an increased dose of LPS (0.5 microgram. kg-1. h-1). A significant reduction in mortality was observed in the ATIII group (0 of 7) compared with the placebo group (4 of 6) (P<0.05, chi2 test) a significant reduction of pulmonary hypertension (placebo, 42.0+/-11. 1 mm Hg; ATIII, 23.6+/-7.5 mm Hg, P<0.05), but no effect on systemic hypotension, was noted in the ATIII group. It was thus concluded that modulation of the procoagulatory state by substitution of ATIII results in a late beneficial antiinflammatory effect in this model of septic shock.
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PMID:Influence of antithrombin III on coagulation and inflammation in porcine septic shock. 1036 91

Protein C, Protein S and Antithrombin III were screened in one hundred patients admitted for abruptio placentae and one hundred women who delivered normally in Dakar university hospital. We found a reduction of Protein S at normal delivery which is linked to hypercoagulation activity during this process. PC and PS were significantly decreased during abruptio placentae in relation with the disseminated intravascular coagulation which was found in our study. We recommend to include these tests to explore aetiologies of abruptio placentae and to confirm their congenital deficit two months after delivery.
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PMID:[Protein C, protein S and antithrombin III at normal delivery and during abruptio placentae]. 1079 88

Antithrombin III (ATIII) has been found to be a marker for DIC and to be of prognostic significance in septic patients. Several studies have shown that administration of ATIII in patients with sepsis related DIC is effective in shortening the duration of DIC. Despite a meta-analysis of randomized controlled trials have shown a significant reduction in 28-day mortality, a prospective randomized double-blind placebo-controlled trial failed to show a significant improvement in overall survival. However the concomitant use of heparin, which does not seem to have an additional beneficial effect, may have obscured the efficacy of ATIII. More studies are needed to understand mechanism of action of ATIII and better define patient population that may benefit from ATIII.
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PMID:Antithrombin III in Sepsis. New evidences and open questions. 1202 61

As the spherical diameter of pulmonary capillaries is smaller than that of neutrophils, increased neutrophil stiffness or conversely, decreased neutrophil deformability is a key step in the initial sequestration of neutrophils within the lungs during inflammatory processes. Antithrombin III (AT) is known to exert a therapeutic effect against disseminated intravascular coagulation, and accumulating evidence suggests that AT also has anti-inflammatory properties. The mechanisms of its anti-inflammatory effects remain unclear, but in a rat endotoxin model, AT apparently inhibited neutrophil sequestration in the lung. In the present in vitro study, therefore, we examined the effect of AT on the deformability of human neutrophils and correlated those findings with their F-actin content. Isolated human neutrophils were stimulated with formyl-Met-Leu-Phe (1 muM, 2 min) in the presence or absence of the alpha, beta, or low heparin-affinity isoforms of AT (1 IU/ml, 20 min), and deformability was evaluated using a filter assay system. Neutrophils were also stained with fluorescein isothiocyanate-phalloidin and subjected to a fluorescein-activated cell sorter scan to assess F-actin content. The results showed that pretreatment with any of the three AT isoforms similarly inhibited the decreased neutrophil deformability and increased F-actin content of stimulated cells. Notably, heparinase had no effect on deformability or F-actin content in the presence or absence of AT, which was somewhat unexpected, as heparin sulfate proteoglycans likely function as AT receptors. These findings suggested that AT inhibits the increase in neutrophil stiffness seen during inflammatory processes by inhibiting actin polymerization via a heparin-independent pathway.
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PMID:Effect of antithrombin III on neutrophil deformability. 1600 Mar 88

Pharmacokinetic (PK) data for antithrombin III (AT) are limited in the critical patients. We therefore performed PK analysis using a two-compartment model and also examined whether plasma AT activity would change depending on two administration methods, AT agent at 500 U/8 h (divided group) or 1,500 U/24 h (combined group) for 3 days, a regulated dosage for disseminated intravascular coagulation (DIC) treatment in Japan, in critical patients with DIC. Clinical prospective randomized study. A high care unit in a university hospital. Twenty-four consecutive critical patients with DIC. Ages ranged from 34 to 91 years. Acute physiology age and chronic health evaluation II scores were 25 to 35. Antithrombin III activities in the combined group caused remarkable transient increases but returned to near the preadministration level 24 h after the infusion. Antithrombin III level in the divided group showed small elevations on each session; therefore, steady increases were found after serial administrations of the agent. On the third day, AT trough activities in the divided group were significantly higher than those in the combined group (P = 0.005). However, peak AT activities in the combined group after AT administration were higher than those in the divided group throughout the study (P = 0.024). Aggravation of bleeding tendency occurred more frequently in the combined group (P = 0.03). Half-life times on the distribution phase in both groups were remarkably shorter than those of previously reported control in congenital AT deficiency. This suggests an increased vascular permeability in the critical patients in this study. Distribution volume in the patients here increased significantly as compared with the previous controls. This is the first PK report using a two-compartment model to demonstrate that remarkable increases in vascular permeability and distribution volume occur in critical patients with DIC, and if the same dose is administered intermittently in such PK situation, AT administration in divided manner can maintain plasma AT trough activity higher than that in the combined method.
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PMID:Differences in antithrombin III activities by administration method in critical patients with disseminated intravascular coagulation: a pharmacokinetic study. 1751 57

Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin that is rapidly progressive and accompanied by vascular collapse and disseminated intravascular coagulation. It usually occurs in children, but this syndrome has also been noted in adults. The purpose of this collective review is to provide modern concepts on the diagnosis and treatment of neonatal purpura fulminans, idiopathic purpura fulminans, and acute infectious purpura fulminans. There are three forms of this disease that are classified by the triggering mechanisms. First, neonatal purpura fulminans is associated with a hereditary deficiency of the natural anticoagulants Protein C and Protein S as well as Antithrombin III. Idiopathic purpura fulminans usually follows an initiating febrile illness that manifests with rapidly progressive purpura. Deficiency of Protein S is considered to be central to the pathogenesis of this form of the disease. The third and most common type of purpura fulminans is acute infectious purpura fulminans. The mortality rate has decreased with better treatment of secondary infections, supportive care, and new treatments, but it remains a disabling condition often requiring major amputations.
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PMID:Modern concepts of the diagnosis and treatment of purpura fulminans. 1865 66

Critically ill children in pediatric intensive care units are commonly indicated for blood transfusion due to many reasons. Children are quite different from adults during growth and development, and that should be taken into consideration. It is very difficult to establish a universal transfusion guideline for critically ill children, especially preterm neonates. Treating underlying disease and targeted replacement therapy are the most effective approaches. Red blood cells are the first choice for replacement therapy in decompensated anemic patients. The critical hemoglobin concentration may be higher in critically ill children for many reasons. Whole blood is used only in the following conditions or diseases: (1) exchange transfusion; (2) after cardiopulmonary bypass; (3) extracorporeal membrane oxygenation; (4) massive transfusion, especially in multiple component deficiency. The characteristics of hemorrhagic diseases are so varied that their therapy should depend on the specific needs associated with the underlying disease. In general, platelet transfusion is not needed when a patient has platelet count greater than 10,000/mm3 and is without active bleeding, platelet functional deficiency or other risk factors such as sepsis. Patients with risk factors or age less than 4 months should be taken into special consideration, and the critical thrombocyte level will be raised. Platelet transfusion is not recommended in patients with immune-mediated thrombocytopenia or thrombocytopenia due to acceleration of platelet destruction without active bleeding or life-threatening hemorrhage. There are many kinds of plasma-derived products, and recombinant factors are commonly used for hemorrhagic patients due to coagulation factor deficiency depending on the characteristics of the diseases. The most effective way to correct disseminated intravascular coagulation (DIC) is to treat the underlying disease. Anticoagulant therapy is very important; heparin is the most common agent used for DIC but the results are usually not satisfactory. Antithrombin III, protein C, or recombinant thrombomodulin has been used successfully to treat this condition. For reducing the risk of organism transmission and adverse reactions resulting from blood transfusion, the following measures have been suggested: (1) replacement therapy using products other than blood (e.g., erythropoietin, iron preparation, granulocyte colony-stimulating factor); (2) special component replacement therapy for specific diseases; (3) autotransfusion; (4) subdividing whole packed blood products into smaller volumes to reduce donor exposure; (5) advances in virus-inactivating procedures. To avoid viral transmission, vapor-heated or pasteurized products and genetic recombinant products are recommended. Cytomegalovirus (CMV)-seronegative blood, leukoreduced and/or irradiated blood are recommended for prevention of CMV infection, graft-versus-host-disease and alloimmunization in neonate and immunocompromised patient transfusion. There is no reason to prescribe a plasma product for nutritional supplementation because of the risk of complications. The principle: complications of transfusion must be avoided, the rate of blood exposure should be reduced and the safety of the transfused agents or components should be maintained must always be kept in mind.
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PMID:Transfusion therapy in critically ill children. 1894 9


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